Human parainfluenza virus (hPIV) and human respiratory syncytial virus (hRSV) are the main causes of acute respiratory diseases during infancy and early childhood worldwide, often requiring hospitalization. Both viruses are also responsible for serious respiratory tract infections in elderly and immunocompromised individuals. No vaccines are currently available to prevent PlV or RSV infection and disease. Aviron proposes to develop live, attenuated vaccines for prevention of disease caused by hPIV and hRSV. A novel bovine PIV3 (bPIV3) virus rescue system, using this proven safe vaccine, was established successfully at Aviron using reverse genetics. In the Phase I SBIR grant period, we used bPIV3 as a virus vector to express the hPIV3 and hRSV (subgroup A) surface glycoproteins. In phase II of the SBIR program, clinical trial material of the two vaccine candidates will be used to evaluate their attenuation, immunogenicity, and efficacy in primates. In addition, the bPIV3 vector will be employed to generate hPIV 1, 2 and hRSV subgroup B vaccines using novel molecular approaches. Our goal is to generate bPIV3-vectored vaccines for hPIV1, 2, 3 and hRSV (A and B) for human clinical trials and commercial development. PROPOSED COMMERCIAL APPLICATIONS: Aviron's goal is to produce live, attenuated hPIV and hRSV vaccines using bPIV3 as a virus vaccine vector for prevention of diseases caused by hPIV 1, 2, and 3 and hRSV(subgroups A and B) infection. These vaccines will fill a current unmet health need.